Photodynamic therapy (PDT) is a treatment method in which a photosensitizer is administered to a subject and utilizes the cytotoxicity of reactive oxygen species including singlet oxygens produced by photoexcitation. PDT has been gathering attention in recent years, owing to the fact that it is a treatment method that is non-invasive and has less tendency of leaving a therapeutic scar.
On the other hand, 5-aminolevulinic acids (also referred to herein as “ALAs”) are a type of natural amino acids comprised in vivo that exist widely in animals or plants or fungi. Although ALAs do not have light sensitivity per se, protoporphyrin IX (hereinafter also referred to as “PpIX”) which is the form metabolically activated by a group of a series of enzymes in the heme biosynthetic pathway in cells is known as a photosensitizer possessing peaks at 410 nm, 510 nm, 545 nm, 580 nm, 630 nm, etc. Accordingly, the research of 5-aminolevulinic acids-photodynamic therapy (hereinafter also referred to as “ALA-PDT”) in which administration of ALM and PDT is carried out in combination to a subject has been brought forward.
Research employing ALA-PDT for treating infection has recently been conducted, and has been gathering attention as an infection treatment method that does not employ an antibiotic (Non-Patent Literature 1). However, the present inventors found that among pathogenic microorganisms that are the cause of infections, there are some which show resistance to ALA-PDT that uses a single ALA. Particularly in Pseudomonas aeruginosa, it was found that those which show resistance to ALA-PDT that uses a single ALA include multi-drug resistant Pseudomonas aeruginosa (MDRP). In other words, the present inventors presented a novel problem in ALA-PDT for treating infection. However, the mechanism in which pathogenic microorganisms show resistance to ALA-PDT has thus far never been elucidated, and this has been the bottleneck to solve this problem.
Numerous occurrences of infection by MDRP have been reported in medical institutions. MDRP is reported to infect those with reduced immunity e.g. due to use of an immunosuppressing agent or acquired immunodeficiency syndrome (AIDS), those that have exhausted physical strength due to e.g. long-term hospitalization or surgery, elderly who are bedridden, and the like to cause severe symptoms, and this has been an extremely large social problem.
A method to use two or more antibiotics in combination to perform infection treatment by synergistic and additive effects thereof has been investigated for these problems (Non-Patent Literature 2). Moreover, numerous researches for finding novel derivatives such as a carbapenem derivative which have superior antibiotic activity against MDRP are also being carried out (Patent Literature 1). However, an effective method for treating infection by MDRP has not yet been established, and prevention of infection has been the main countermeasure.
Moreover, even if an effective antibiotic or a combination of antibiotics against MDRP is developed in the future, the emergence of Pseudomonas aeruginosa that show further resistance to these agents is inevitably predicted. For the above reasons, development of a novel method for treating MDRP that does not rely solely on antibiotics has been strongly demanded.